The goal of this project is to understand the mechanisms by which gonadotropin-releasing hormone (GnRH) stimulates the secretion of luteinizing hormone (LH). Recently, a new set of GnRH neurons have been described in embryonic primate brain. Using in situ hybridization, we confirmed the presence of GnRH mRNA-expressing neurons in the medial forebrain of adult pigtailed macaques (Macaca nemestina). These neurons appear to correspond to the neurons that control reproductive function. We also found many GnRH mRNA-expressing neurons in lateral forebrain areas. In rats, the neuropeptide galanin is coexpressed in a subset of GnRH neurons that control reproductive function, and this galanin may act to facilitate LH secretion. We found that galanin mRNA is expressed in a subset of the lateral GnRH mRNA-expressing neurons in pigtailed macaques. These results suggest that primates have GnRH mRNA-expressing neurons localized outside the medial forebrain, whose function is currently unknown, and that galanin may be a cotransmitter with GnRH in a subset of these neurons. We are also examining the effects of leptin on the reproductive axis in primates. In rodents, leptin regulates body weight and metabolism and appears to act as a metabolic signal to the reproductive axis. We found that leptin reverses fasting-induced suppression of LH in male rhesus macaques (Macaca mulatta), suggesting that leptin plays a similar role in primates. In addition, we have identified leptin receptor (Ob-R) mRNA-expressing cells in hypothalamic areas that control reproduction and feeding in monkeys and found that Ob-R mRNA is expressed in proopiomelanocortin and neuropeptide Y neurons but not in GnRH neurons. These results suggest that the effects of leptin on LH secretion may be mediated by neuropeptide Y and products of the proopiomelanocortin gene.